Antengene's AACR 2025 Breakthroughs: TCE 2.0 and Synthetic Lethality Drive Oncology Innovation

Antengene Corporation’s four poster presentations at the 2025 American Association for Cancer Research (AACR) Annual Meeting have positioned the company as a leader in next-generation oncology therapies. Two of these studies, centered on its proprietary AnTenGager TCE 2.0 platform and synthetic lethality strategies, highlight breakthroughs with the potential to address critical unmet needs in cancer treatment. These advancements, coupled with Antengene’s robust pipeline and strategic focus on global drug development, suggest significant growth opportunities for investors.

ATG-110: A New Frontier in MSS Colorectal Cancer

The first poster detailed ATG-110, a “2+1” T cell engager (TCE) targeting LY6G6D, a surface antigen highly expressed in microsatellite stable (MSS) colorectal cancer (CRC). MSS CRC accounts for over 90% of CRC cases and is notoriously resistant to checkpoint inhibitors like PD-1/PD-L1 therapies. Antengene’s AnTenGager TCE 2.0 platform addresses this gap by designing a TCE that binds LY6G6D with high specificity while minimizing off-target CD3 activation—a critical safety improvement over earlier TCEs.

Preclinical data showed ATG-110’s remarkable efficacy:
- In vitro: Potent T cell-mediated cytotoxicity against both high- and low-LY6G6D-expressing tumor cells (IC50 in single-digit pM).
- In vivo: Complete tumor regression in HT55 MSS CRC models and significant suppression in SW480 models, with minimal cytokine release syndrome (CRS).

Antengene plans to initiate Phase 1/2 trials for ATG-110 in late 2025, targeting MSS CRC patients. This could mark a major shift in treatment paradigms for one of the deadliest cancer subtypes.

ATG-042: Exploiting Synthetic Lethality in MTAPnull Cancers

The second poster focused on ATG-042, a first-in-class PRMT5 inhibitor selective for tumors lacking MTAP (methylthioadenosine phosphorylase). MTAP loss creates a synthetic lethal vulnerability by disrupting the PRMT5-MTA complex, enabling ATG-042 to kill cancer cells while sparing healthy tissues. This selectivity addresses a major drawback of non-selective PRMT5 inhibitors, which often cause severe hematological toxicity.

Key preclinical findings include:
- Efficacy: Robust anti-proliferative activity (IC50 10–100 nM) in MTAPnull cell lines (e.g., LU99, U87MG) with no effect on MTAP wild-type cells.
- In vivo activity: Single-agent tumor regression in subcutaneous and orthotopic models, including HCT116-MTAPko and U87MG-luc (glioblastoma).
- Pharmacokinetics: Excellent oral bioavailability, brain penetration (51% brain/plasma ratio), and metabolic stability, supporting clinical translation.

Antengene aims to advance ATG-042 into Phase 1 trials in 2025, targeting MTAPnull malignancies such as glioblastoma and colorectal cancer. The global market for MTAPnull therapies could exceed $2 billion by 2030, driven by high unmet need in these aggressive cancers.

Strategic Pipeline and Companion Diagnostic

Antengene’s pipeline includes nine oncology assets, six with global rights, and it has secured 31 IND approvals across Asia. The companion diagnostic ATG-1144 (CD24 antibody) further strengthens its value proposition by enabling patient stratification for CD24-expressing tumors (50–80% of lung, breast, bladder, ovarian, or liver cancers). This precision medicine approach reduces trial costs and improves outcomes.

Conclusion: A Pivotal Moment for Antengene

Antengene’s AACR 2025 presentations underscore its position as a leader in first-in-class oncology therapies. The AnTenGager TCE 2.0 platform and MTAPnull synthetic lethality strategy address critical gaps in MSS CRC and MTAPnull cancers, markets with combined annual treatment costs exceeding $10 billion. With Phase 1 trials for both ATG-110 and ATG-042 planned for 2025, the company is poised to deliver transformative data within 12–18 months.

Antengene’s 31 IND approvals and six globally licensed assets further validate its execution capability. If these programs meet their endpoints, the company could accelerate toward NDA submissions by 2027–2028, unlocking significant commercial value. For investors, Antengene represents a rare opportunity to capitalize on two groundbreaking platforms in a sector with high unmet need and limited competition. The next 12 months will be pivotal—a phase I readout success could catalyze a 20–30% stock premium, given the therapies’ clinical and commercial potential.

Antengene’s AACR 2025 milestones are not just scientific achievements but clear roadmaps to future growth, making it a compelling play in oncology innovation.